WO2013077641A1 - Skin repair enhancer containing growth factors - Google Patents
Skin repair enhancer containing growth factors Download PDFInfo
- Publication number
- WO2013077641A1 WO2013077641A1 PCT/KR2012/009919 KR2012009919W WO2013077641A1 WO 2013077641 A1 WO2013077641 A1 WO 2013077641A1 KR 2012009919 W KR2012009919 W KR 2012009919W WO 2013077641 A1 WO2013077641 A1 WO 2013077641A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- growth factor
- skin
- skin regeneration
- ppm
- regeneration
- Prior art date
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to a skin regeneration accelerator comprising a growth factor
- the skin acts as a shield to protect the body from the outside. If such a wound occurs on the skin, the healing is achieved by the natural healing action of the living body.
- the wound healing process is divided into four stages: inflammatory, re-epithelial, proliferative and mature stages.
- inflammatory re-epithelial
- proliferative mature stages.
- immune cells migrated from blood vessels appear at the wound site, which usually progress briefly in the absence of significant infection.
- granular tissues including fibroblasts, inflammatory cells, and extracellular matrix components, such as immaturity collagen, fibronectin, or hyaluronic acid, are placed on the wound site. Is formed. The rapid filling and organization of these granular tissues is a key to wound healing.
- the exfoliated wound surface is then covered by a layer of keratinocytes, creating a new epidermis and reconstructing the epidermal layer. This means that in the process of wound healing, promoting the regeneration of fibroblasts or keratinocytes can quickly heal skin wounds and minimize scarring.
- Patent Document 1 Korean Patent Publication No. 10-2010-0098298 (Published September 9, 2010)
- the present invention seeks to provide agents that promote skin regeneration and specifically promote skin wound and burn healing.
- the present invention is to provide a cosmetic composition and a pharmaceutical composition having an excellent skin regeneration promoting effect, including the skin regeneration accelerator as described above.
- EGF epidermal growth factor
- PDGF-AA platelet-derived growth factor-AA
- IGF-1 insulin-like growth factor-1
- Another aspect of the present invention provides a cosmetic composition and a pharmaceutical composition comprising the skin regeneration accelerator.
- the preparations according to the invention comprise epithelial growth factor, platelet derived growth factor-AA and insulin-like growth factor-1, and optionally further comprise one or more growth factors of transforming growth factor- ⁇ and fibroblast growth factor. As a result, it has an excellent skin regeneration effect, further promotes skin wound and burn healing, and minimizes scarring.
- 1 is a graph showing the effect of growth factors or combinations thereof on human keratinocyte regeneration.
- FIG. 2 is a graph showing the effect of growth factors or combinations thereof on human fibroblast regeneration.
- Figure 3 is a diagram showing the observation of the extent to which the growth factors or combinations of artificial skin regeneration.
- skin refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
- One aspect of the present invention is epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1, Insulin It provides a skin regeneration accelerator comprising -like growth factor-1).
- Another aspect of the present invention provides a skin regeneration promoter further comprising one or more growth factors of transforming growth factor beta (TGF- ⁇ ) and fibroblast growth factor (FGF).
- TGF- ⁇ transforming growth factor beta
- FGF fibroblast growth factor
- the growth factors promote growth and regeneration of keratinocytes and fibroblasts.
- formulations comprising the same may promote skin regeneration, further promoting skin wound and burn healing, and reducing scars.
- growth factor refers to a polypeptide that promotes the division, growth and differentiation of multiple cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor- 1 (IGF-1), transforming growth factor- ⁇ (TGF- ⁇ ) or fibroblast growth factor (FGF), but is not limited thereto.
- EGF epidermal growth factor
- PDGF-AA platelet derived growth factor-AA
- IGF-1 insulin-like growth factor- 1
- TGF- ⁇ transforming growth factor- ⁇
- FGF fibroblast growth factor
- Epidermal growth factor is a growth factor that promotes growth, differentiation and division of epithelial cells by secreting not only from the skin but also from mucous membranes such as the oral cavity and gastrointestinal tract. It is known to prevent tissue damage from the factor.
- Platelet derived growth factor-AA is a growth factor that has an important effect on mesenchymal stem cell division during development. In addition to the developmental process, the adult is known to promote the growth, division and migration of mesenchymal-derived cells, and in particular, to promote fibroblast division in the skin.
- Insulin-like growth factor-1 is basically a growth factor that acts similar to insulin in the body. Examples include skeletal muscle cells, bone cells, chondrocytes, liver cells, kidney cells, nerve cells, skin cells, and hematopoietic cells. It is known to promote the growth of all kinds of cells in the body. In addition, since the growth factor plays an important role in growth, growth deficiency may appear when the growth factor is deficient in infancy, and it is known to play a role in regulating energy assimilation after growth.
- Transforming growth factor- ⁇ is a growth factor that plays a role in maintaining cell homeostasis by controlling cell division and differentiation.
- induction of apoptosis (apoptosis) in a number of cells, epithelial cells and cancer cells act as a factor that inhibits division. It is known that the skin may have a whitening effect by inhibiting tyrosinase.
- Fibroblast growth factor promotes the growth and division of epithelial cells, and is superior to vascular endothelial growth factor (VEGF).
- VEGF vascular endothelial growth factor
- this growth factor is known to be involved as an important growth factor in the wound healing process by making new blood vessels in the wound site, proliferating fibroblasts to create granulation tissue.
- Skin regeneration promoter comprising epidermal growth factor, platelet-derived growth factor-AA, and insulin-like growth factor-1 according to one aspect of the present invention
- each growth factor 1-5: 1-5: 1-5, specifically 1-3 may be included in the weight ratio of 1 to 3: 1 to 3, more specifically 1 to 2: 1 to 2: 1-2.
- a skin regeneration promoter comprising epidermal growth factor, platelet derived growth factor-AA, insulin-like growth factor-1, transforming growth factor- ⁇ and fibroblast growth factor may be selected from each growth factor.
- -5: 1-5: 1-5: 1-5: 1-5: 1-5: 1-5, specifically 1-3: 1-3: 1-3, 1-3: 1-3, more specifically 1-2: 1- 2: 1 to 2: 1 to 2: may be included in the weight ratio of 1-2.
- Skin regeneration accelerator according to one aspect of the present invention is 1 ⁇ 10 -6 to 1 ⁇ 10 4 % by weight, specifically 1 ⁇ 10 -4 to 1 ⁇ 10 3 % by weight, more specifically based on the total weight of the skin regeneration accelerator 1 ⁇ 10 ⁇ 2 to 1 ⁇ 10 2 weight percent of growth factors or combinations thereof.
- When included in the above range is not only suitable for showing the intended effect of the present invention, it can satisfy both the stability and safety of the accelerator, it may be appropriate to include in the above range in terms of cost-effectiveness.
- One aspect of the present invention provides a cosmetic composition comprising a skin regeneration accelerator comprising the growth factor.
- the cosmetic composition may have a skin regeneration effect, and in particular, may heal skin wounds and burns and reduce scars.
- Cosmetic compositions according to the invention may be provided in all formulations suitable for topical application.
- it may be provided in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a foam, or an aerosol composition.
- Compositions of such formulations may be prepared according to conventional methods in the art.
- the cosmetic composition according to the present invention may include other ingredients in addition to the above-mentioned substances within the range not impairing the main effect, preferably giving a synergistic effect to the main effect.
- the cosmetic composition according to the present invention may further include a moisturizer, an emulsifier, a surfactant, a ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, organic and inorganic pigments, flavors, coolants, or limiting agents. have.
- the blending amount of the above components can be easily selected by those skilled in the art within the range that does not impair the object and effect of the present invention, the blending amount may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight based on the total weight of the composition have.
- One aspect of the invention provides a pharmaceutical composition comprising a skin regeneration accelerator comprising the growth factor.
- the pharmaceutical composition may have a skin regeneration effect, and specifically may have a skin wound and burn healing and amelioration effect and a scar reduction effect.
- composition according to one aspect of the present invention may be administered orally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.
- Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, fine granules, solutions, emulsions or pellets, but are not limited thereto. It is not. These formulations may contain, in addition to the active ingredient, diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose or glycine), glidants (e.g. silica, talc, stearic acid or polyethylene glycol), or binders (e.g. magnesium aluminum Silicates, starch pastes, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose or polyvinylpyrrolidine). It may optionally contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, or sweeteners.
- the tablets can be prepared by conventional mixing, granulating or coating methods.
- Formulations for parenteral administration may be, but are not limited to, injections, drops, lotions, ointments, gels, creams, suspensions, emulsions, suppositories, patches or sprays.
- the active ingredient of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Dosage determination based on these factors is within the level of one skilled in the art and its daily dosage may be, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / kg. May be, but is not limited to.
- One aspect of the present invention provides a food composition comprising the skin regeneration accelerator.
- the food composition has a skin regenerating effect and specifically can heal skin wounds and burns and reduce scars.
- the formulation of the food composition is not particularly limited, but may be, for example, formulated into a liquid such as tablets, granules, powders, drinks, caramels, gels, bars, and the like.
- the food composition of each formulation may be suitably selected by a person skilled in the art according to the formulation or purpose of use in addition to the active ingredient, and may be synergistic when applied simultaneously with other raw materials.
- the daily dosage of the active ingredient is within the level of those skilled in the art, the daily dosage of which is for example from 0.1 mg / kg / day to 5000 mg / kg / day, more specifically from 50 mg / kg / day to 500 mg / kg / day, but is not limited thereto, and may vary depending on various factors such as age, health condition, and complications of the subject to be administered.
- HaCaT cells human-derived keratinocyte cell lines, were treated with 10% fetal bovine serum (JRH Bioscience, Tokyo, Japan), 100 mg / ml penicillin and 100 mg / ml streptomycin (both GIBCO , DMEM medium (Invitrogen, Carlsbad, Calif.) was added at 37 °C, 5% CO 2 conditions. Incubate the cells in a 12-well plate at 3.5 X 10 5 per well, wait overnight for the cells to adhere to the wall, wash the cells once with PBS and scrape the cells with a 200 ⁇ l pipette tip. I made a vertical scratch in the middle.
- Wound Fill Rate (%) ⁇ (0 Hour Scratch Area-24 Hour Scratch Area) / 0 Hour Scratch Area ⁇ X 100
- EGF TGF- ⁇ PDGF-AA bFGF IGF-1 Sum Control 0 0 0 0 0 0.06 ppm EGF 0.06 ppm 0 0 0 0.06 ppm TGF- ⁇ 0 0.06 ppm 0 0 0 0.06 ppm PDGF-AA 0 0 0.06 ppm 0 0 0.06 ppm bFGF 0 0 0 0.06 ppm 0 0.06 ppm IGF-1 0 0 0 0 0.06 ppm 0.06 ppm EGF + TGF- ⁇ 0.03ppm 0.03ppm 0 0 0 0.06 ppm EGF + PDGF-AA 0.03ppm 0 0.03ppm 0 0.06 ppm EGF + FGF 0.03ppm 0 0 0.03ppm 0 0.06 ppm EGF + IGF-1 0.03ppm 0 0 0 0.03ppm 0.06 ppm TGF- ⁇ + PDGF
- each growth factor and combination of growth factors promotes the regeneration of keratinocytes.
- a combination of epithelial growth factor and platelet derived growth factor-AA a combination of epithelial growth factor and platelet derived growth factor-AA, a combination of epithelial growth factor, transforming growth factor- ⁇ and platelet derived growth factor-AA.
- Combination of epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth factor-1, and combination of transforming growth factor- ⁇ , platelet-derived growth factor-AA and insulin-like growth factor-1 It showed a cell regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
- each growth factor and combination of growth factors promotes the regeneration of fibroblasts.
- a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth The combination of factor-1 and the combination of epithelial growth factor, platelet derived growth factor-AA and fibroblast growth factor showed a particularly good fibroblast regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
- Infrared skin is irradiated with a CO 2 laser to create a thermal wound, which is a combination of epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1).
- EGF epidermal growth factor
- PDGF-AA platelet-derived growth factor-AA
- IGF-1 insulin-like growth factor-1
- the EpiDermFT Full Thickness Skin Model (MatTek) was grown in growth media for artificial skin for 4 days, and CO 2 laser (eCO2, Lutronic) was applied to the artificial skin for tip type 120, 40mJ.
- the wound was made by treatment with an energy of 8 mm in size and a density of 150 spots / cm 2 .
- a growth factor composition consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1) having a total skin concentration of 3 ppm or less. (GF Mix.) And DMEM / F12 media containing 4 ppm epidermal growth factor (EGF) and DMEM / F12 media (control) without growth factor, respectively.
- epithelial growth factor EGF
- platelet-derived growth factor-AA PDGF-AA
- artificial base cells treated with a growth factor composition (GF Mix.)
- GF Mix Composed of a combination of insulin-like growth factor-1 (IGF-1) at a concentration of 3 ppm or less in total, as well as the basement membrane (dermis / epidermal border) and dermis.
- IGF-1 insulin-like growth factor-1
- GF Mix Consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1), which is an embodiment of the present invention.
- EGF epidermal growth factor
- PDGF-AA platelet derived growth factor-AA
- IGF-1 insulin-like growth factor-1
- Ointments are prepared according to conventional methods with the compositions described in the table below.
- a cream is prepared according to a conventional method with the composition described in the table below.
- Epithelial growth factor Epithelial growth factor, insulin-like growth factor-1, platelet-derived growth factor-AA and fibroblast growth factor 8.0 Polyethylene Glycol Monostearate 2.0 Glycerin Monostearate 5.0 Cetyl alcohol 4.0 Squalene 3.0 Tri2-ethylhexaneglyceryl 6.0 Sphingolipid 1.0 1,3-butylene glycol 7.0 Purified water Remaining amount
- Epithelial Cell Growth Factor Epithelial Cell Growth Factor, Platelet-derived Growth Factor-AA and Insulin-like Growth Factor-1 ... 100 g
- the above ingredients are mixed according to a conventional method for preparing a health beverage, then stirred and heated at 85 ° C. for about 1 hour, and then the resulting solution is filtered and sterilized.
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Abstract
Disclosed is a skin repair enhancer containing EGF (epidermal growth factor), PDGF-AA (platelet-derived growth factor-AA) and IGF-1 (insulin-like growth factor 1).
Description
본 발명은 성장 인자를 포함하는 피부 재생 촉진제에 관한 것이다The present invention relates to a skin regeneration accelerator comprising a growth factor
피부는 외부로부터 신체를 보호하는 방어막 역할을 한다. 이러한 피부에 상처가 생기면 생체의 자연 치유 작용에 의해 그 치유가 이루어진다.The skin acts as a shield to protect the body from the outside. If such a wound occurs on the skin, the healing is achieved by the natural healing action of the living body.
상처 치유 과정은 크게 염증기, 재상피화기, 증식기 및 성숙기의 4단계로 구분된다. 염증기에는 혈관에서 이동한 면역 세포들이 상처 부위에 출현하며, 이는 중대한 감염이 없는 경우 일반적으로 짧게 진행된다.The wound healing process is divided into four stages: inflammatory, re-epithelial, proliferative and mature stages. In the inflammatory phase, immune cells migrated from blood vessels appear at the wound site, which usually progress briefly in the absence of significant infection.
증식기에는 섬유아세포(fibroblasts), 염증성 세포(inflammatory cells)와 함께 미성숙 콜라겐(immaturity collagen), 피브로넥틴(fibronectin) 또는 히알루론산(hyaluronic acid) 등의 세포외기질 구성 요소들을 포함하는 과립 조직들이 상처 부위에 형성된다. 이 과립 조직들이 상처 부위를 빠르게 채우고 조직적인 구조를 갖추는 것이 상처 치유의 중요한 관건이 된다. 이후 벗겨진 상처 표면이 각질형성세포(keratinocytes)층에 의해 덮이면서 새로운 표피가 생성되고 상피층이 재건된다. 이는 상처 치유 과정에 있어, 섬유아세포 또는 각질형성세포의 재생을 촉진시키면 피부 상처 치유가 신속하게 이루어져 흉터가 최소화될 수 있음을 의미한다.In the proliferative phase, granular tissues, including fibroblasts, inflammatory cells, and extracellular matrix components, such as immaturity collagen, fibronectin, or hyaluronic acid, are placed on the wound site. Is formed. The rapid filling and organization of these granular tissues is a key to wound healing. The exfoliated wound surface is then covered by a layer of keratinocytes, creating a new epidermis and reconstructing the epidermal layer. This means that in the process of wound healing, promoting the regeneration of fibroblasts or keratinocytes can quickly heal skin wounds and minimize scarring.
[선행기술문헌][Preceding technical literature]
[특허문헌][Patent Documents]
(특허문헌 1) 한국특허공개 제10-2010-0098298호(2010.09.06. 공개) 명세서(Patent Document 1) Korean Patent Publication No. 10-2010-0098298 (Published September 9, 2010)
본 발명은 피부 재생을 촉진하며, 구체적으로 피부 상처 및 화상 치유를 촉진하는 제제를 제공하고자 한다. 또한 본 발명은 상기와 같은 피부 재생 촉진제를 포함하여 우수한 피부 재생 촉진 효과를 가지는 화장료 조성물 및 약학 조성물을 제공하고자 한다.The present invention seeks to provide agents that promote skin regeneration and specifically promote skin wound and burn healing. In addition, the present invention is to provide a cosmetic composition and a pharmaceutical composition having an excellent skin regeneration promoting effect, including the skin regeneration accelerator as described above.
본 발명의 일측면은 상피 세포 성장 인자(EGF, Epidermal growth factor), 혈소판 유래 성장 인자-AA(PDGF-AA, Platelet-derived growth factor-AA) 및 인슐린 유사 성장 인자-1(IGF-1, Insulin-like growth factor 1)을 포함하는 피부 재생 촉진제를 제공한다.One aspect of the present invention is epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1, Insulin It provides a skin regeneration accelerator comprising -like growth factor 1).
본 발명의 다른 일측면은 상기 피부 재생 촉진제를 포함하는 화장료 조성물 및 약학 조성물을 제공한다.Another aspect of the present invention provides a cosmetic composition and a pharmaceutical composition comprising the skin regeneration accelerator.
본 발명에 따른 제제는 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1을 포함함으로써, 또한 선택적으로 형질 전환 성장 인자-β 및 섬유아세포 성장 인자 중 하나 이상의 성장 인자를 더 포함함으로써, 우수한 피부 재생 효과, 나아가 피부 상처 및 화상 치유를 촉진하며, 흉터를 최소화하는 효과를 가진다.The preparations according to the invention comprise epithelial growth factor, platelet derived growth factor-AA and insulin-like growth factor-1, and optionally further comprise one or more growth factors of transforming growth factor-β and fibroblast growth factor. As a result, it has an excellent skin regeneration effect, further promotes skin wound and burn healing, and minimizes scarring.
도 1은 성장 인자 또는 그들의 조합이 인간 각질형성세포 재생에 미치는 영향을 나타낸 그래프이다.1 is a graph showing the effect of growth factors or combinations thereof on human keratinocyte regeneration.
도 2는 성장 인자 또는 그들의 조합이 인간 섬유아세포 재생에 미치는 영향을 나타낸 그래프이다.2 is a graph showing the effect of growth factors or combinations thereof on human fibroblast regeneration.
도 3은 성장 인자 또는 그들의 조합이 인공피부를 재생시킨 정도를 관찰하여 나타낸 도이다.Figure 3 is a diagram showing the observation of the extent to which the growth factors or combinations of artificial skin regeneration.
본 명세서에서 "피부"라 함은, 동물의 체표를 덮는 조직을 의미하는 것으로서, 얼굴 또는 바디 등의 체표를 덮는 조직뿐만 아니라, 두피와 모발을 포함하는 최광의의 개념이다.As used herein, the term "skin" refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
본 발명의 일측면은 상피 세포 성장 인자(EGF, Epidermal growth factor), 혈소판 유래 성장 인자-AA(PDGF-AA, Platelet-derived growth factor-AA) 및 인슐린 유사 성장 인자-1(IGF-1, Insulin-like growth factor-1)을 포함하는 피부 재생 촉진제를 제공한다. 본 발명의 다른 일측면은 형질 전환 성장 인자-β(TGF-β, Transforming growth factor beta) 및 섬유아세포 성장 인자(FGF, Fibroblast growth factor) 중 하나 이상의 성장 인자를 더 포함하는 피부 재생 촉진제를 제공한다. 상기 성장 인자들은 각질형성세포와 섬유아세포의 성장 및 재생을 촉진한다. 따라서 이를 포함하는 제제는 피부 재생을 촉진하고, 나아가 피부 상처 및 화상 치유를 촉진하며, 흉터를 감소시킬 수 있다.One aspect of the present invention is epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1, Insulin It provides a skin regeneration accelerator comprising -like growth factor-1). Another aspect of the present invention provides a skin regeneration promoter further comprising one or more growth factors of transforming growth factor beta (TGF-β) and fibroblast growth factor (FGF). . The growth factors promote growth and regeneration of keratinocytes and fibroblasts. Thus formulations comprising the same may promote skin regeneration, further promoting skin wound and burn healing, and reducing scars.
본 명세서에서, “성장 인자”는 여러 세포의 분열, 성장 및 분화를 촉진하는 폴리펩티드를 의미하며, 상피 세포 성장 인자(EGF), 혈소판 유래 성장 인자-AA(PDGF-AA), 인슐린 유사 성장 인자-1(IGF-1), 형질 전환 성장 인자-β(TGF-β) 또는 섬유아세포 성장 인자(FGF)를 포함하나, 이에 제한되는 것은 아니다.As used herein, “growth factor” refers to a polypeptide that promotes the division, growth and differentiation of multiple cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor- 1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor (FGF), but is not limited thereto.
상피 세포 성장 인자는 피부뿐만 아니라 구강, 위장과 같은 점막에서도 분비되어 상피 세포의 성장, 분화 및 분열을 촉진하는 성장 인자로, 상피 조직에 손상이 가해지면 이를 빠르게 회복시켜 외부 감염원이나 위액과 같은 내부 인자로부터 조직이 손상되는 것을 막는 것으로 알려져 있다.Epidermal growth factor is a growth factor that promotes growth, differentiation and division of epithelial cells by secreting not only from the skin but also from mucous membranes such as the oral cavity and gastrointestinal tract. It is known to prevent tissue damage from the factor.
혈소판 유래 성장 인자-AA는 발생 과정에서 간엽 줄기세포 분열에 중요한 영향을 미치는 성장 인자이다. 발생 과정뿐 아니라 성체에서도 간엽 유래 세포의 성장, 분열 및 이동을 촉진하고, 특히 피부에서는 섬유아세포의 분열을 촉진한다고 알려져 있다.Platelet derived growth factor-AA is a growth factor that has an important effect on mesenchymal stem cell division during development. In addition to the developmental process, the adult is known to promote the growth, division and migration of mesenchymal-derived cells, and in particular, to promote fibroblast division in the skin.
인슐린 유사 성장 인자-1은 기본적으로 체내에서 인슐린과 유사한 작용을 하는 성장 인자로, 골격근 세포, 골 세포, 연골 세포, 간 세포, 신장 세포, 신경 세포, 피부 세포, 조혈 세포 등을 예로 들 수 있는 체내 모든 종류의 세포의 성장을 증진시킬 수 있다고 알려져 있다. 또한 본 성장 인자는 성장에 중요한 역할을 하므로 유아기 때 본 성장 인자가 결핍되면 성장 장애가 나타날 수 있으며, 성장이 끝난 후에는 에너지 동화를 조절하는 역할을 하는 것으로 알려져 있다.Insulin-like growth factor-1 is basically a growth factor that acts similar to insulin in the body. Examples include skeletal muscle cells, bone cells, chondrocytes, liver cells, kidney cells, nerve cells, skin cells, and hematopoietic cells. It is known to promote the growth of all kinds of cells in the body. In addition, since the growth factor plays an important role in growth, growth deficiency may appear when the growth factor is deficient in infancy, and it is known to play a role in regulating energy assimilation after growth.
형질 전환 성장 인자-β는 세포의 분열, 분화를 조절하여 세포의 항상성을 유지하는 역할을 하는 성장 인자이다. 또한 여러 세포에서 아폽토시스(apoptosis)를 유도하며, 상피 세포와 암세포에서는 분열을 억제하는 인자로 작용한다. 피부에서는 티로시나제를 억제하여 미백 효과를 나타낼 수 있는 것으로 알려져 있다.Transforming growth factor-β is a growth factor that plays a role in maintaining cell homeostasis by controlling cell division and differentiation. In addition, induction of apoptosis (apoptosis) in a number of cells, epithelial cells and cancer cells act as a factor that inhibits division. It is known that the skin may have a whitening effect by inhibiting tyrosinase.
섬유아세포 성장 인자는 상피 세포의 성장, 분열을 촉진하여 혈관내피세포 성장 인자(VEGF)보다 혈관 신생 효과가 더 뛰어나다. 또한 본 성장 인자는 상처 부위에 새로운 혈관을 만들고, 섬유아세포를 증식시켜 육아 조직을 만들어 상처 회복 과정에 중요한 성장 인자로 관여하는 것으로 알려져 있다.Fibroblast growth factor promotes the growth and division of epithelial cells, and is superior to vascular endothelial growth factor (VEGF). In addition, this growth factor is known to be involved as an important growth factor in the wound healing process by making new blood vessels in the wound site, proliferating fibroblasts to create granulation tissue.
본 발명의 일측면에 따른 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1을 포함하는 피부 재생 촉진제는 각 성장 인자를 1~5 : 1~5 : 1~5, 구체적으로 1~3 : 1~3 : 1~3, 더 구체적으로 1~2 : 1~2 : 1~2의 중량비로 포함할 수 있다. 본 발명의 다른 일측면에 따른 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA, 인슐린 유사 성장 인자-1, 형질 전환 성장 인자-β 및 섬유아세포 성장 인자를 포함하는 피부 재생 촉진제는 각 성장 인자를 1~5 : 1~5 : 1~5 : 1~5 : 1~5, 구체적으로 1~3 : 1~3 : 1~3 : 1~3 : 1~3, 더 구체적으로 1~2 : 1~2 : 1~2 : 1~2 : 1~2의 중량비로 포함할 수 있다.Skin regeneration promoter comprising epidermal growth factor, platelet-derived growth factor-AA, and insulin-like growth factor-1 according to one aspect of the present invention, each growth factor 1-5: 1-5: 1-5, specifically 1-3 may be included in the weight ratio of 1 to 3: 1 to 3, more specifically 1 to 2: 1 to 2: 1-2. In accordance with another aspect of the present invention, a skin regeneration promoter comprising epidermal growth factor, platelet derived growth factor-AA, insulin-like growth factor-1, transforming growth factor-β and fibroblast growth factor may be selected from each growth factor. -5: 1-5: 1-5: 1-5: 1-5, specifically 1-3: 1-3: 1-3, 1-3: 1-3, more specifically 1-2: 1- 2: 1 to 2: 1 to 2: may be included in the weight ratio of 1-2.
본 발명의 일측면에 따른 피부 재생 촉진제는 피부 재생 촉진제 전체 중량을 기준으로 1×10-6 내지 1×104 중량%, 구체적으로 1×10-4 내지 1×103 중량%, 더 구체적으로 1×10-2 내지 1×102 중량%의 성장 인자 또는 그들의 조합을 포함할 수 있다. 상기 범위로 포함할 경우 본 발명의 의도한 효과를 나타내기에 적절할 뿐만 아니라, 촉진제의 안정성 및 안전성을 모두 만족할 수 있으며, 비용 대비 효과의 측면에서도 상기 범위로 포함하는 것이 적절할 수 있다.Skin regeneration accelerator according to one aspect of the present invention is 1 × 10 -6 to 1 × 10 4 % by weight, specifically 1 × 10 -4 to 1 × 10 3 % by weight, more specifically based on the total weight of the skin regeneration accelerator 1 × 10 −2 to 1 × 10 2 weight percent of growth factors or combinations thereof. When included in the above range is not only suitable for showing the intended effect of the present invention, it can satisfy both the stability and safety of the accelerator, it may be appropriate to include in the above range in terms of cost-effectiveness.
본 발명의 일측면은 상기 성장 인자를 포함하는 피부 재생 촉진제를 포함하는 화장료 조성물을 제공한다. 상기 화장료 조성물은 피부 재생 효과를 가질 수 있으며, 구체적으로 피부 상처 및 화상을 치유하고 흉터를 감소시킬 수 있다.One aspect of the present invention provides a cosmetic composition comprising a skin regeneration accelerator comprising the growth factor. The cosmetic composition may have a skin regeneration effect, and in particular, may heal skin wounds and burns and reduce scars.
본 발명에 따른 화장료 조성물은 국소 적용에 적합한 모든 제형으로 제공될 수 있다. 예를 들면, 용액, 수상에 유상을 분산시켜 얻은 에멀젼, 유상에 수상을 분산시켜 얻은 에멀젼, 현탁액, 고체, 겔, 분말, 페이스트, 포말(foam) 또는 에어로졸 조성물의 제형으로 제공될 수 있다. 이러한 제형의 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다.Cosmetic compositions according to the invention may be provided in all formulations suitable for topical application. For example, it may be provided in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a foam, or an aerosol composition. Compositions of such formulations may be prepared according to conventional methods in the art.
본 발명에 따른 화장료 조성물은 상기한 물질 이외에 주 효과를 손상시키지 않는 범위 내에서, 바람직하게는 주 효과에 상승 효과를 줄 수 있는 다른 성분들을 포함할 수 있다. 또한 본 발명에 따른 화장료 조성물은 보습제, 에몰리언트제, 계면 활성제, 자외선 흡수제, 방부제, 살균제, 산화 방지제, pH 조정제, 유기 및 무기 안료, 향료, 냉감제 또는 제한(制汗)제를 더 포함할 수 있다. 상기 성분의 배합량은 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 당업자가 용이하게 선정 가능하며, 그 배합량은 조성물 전체 중량을 기준으로 0.01 내지 5 중량%, 구체적으로 0.01 내지 3 중량%일 수 있다.The cosmetic composition according to the present invention may include other ingredients in addition to the above-mentioned substances within the range not impairing the main effect, preferably giving a synergistic effect to the main effect. In addition, the cosmetic composition according to the present invention may further include a moisturizer, an emulsifier, a surfactant, a ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, organic and inorganic pigments, flavors, coolants, or limiting agents. have. The blending amount of the above components can be easily selected by those skilled in the art within the range that does not impair the object and effect of the present invention, the blending amount may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight based on the total weight of the composition have.
본 발명의 일측면은 상기 성장 인자를 포함하는 피부 재생 촉진제를 포함하는 약학 조성물을 제공한다. 상기 약학 조성물은 피부 재생 효과를 가질 수 있으며, 구체적으로 피부 상처 및 화상 치유 및 개선 효과, 흉터 감소 효과를 가질 수 있다.One aspect of the invention provides a pharmaceutical composition comprising a skin regeneration accelerator comprising the growth factor. The pharmaceutical composition may have a skin regeneration effect, and specifically may have a skin wound and burn healing and amelioration effect and a scar reduction effect.
본 발명의 일측면에 따른 약학 조성물은 경구, 직장, 국소, 경피, 정맥 내, 근육 내, 복강 내, 피하 등으로 투여될 수 있다.The pharmaceutical composition according to one aspect of the present invention may be administered orally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.
경구 투여를 위한 제형은 정제(錠劑), 환제(丸劑), 연질 및 경질 캅셀제, 과립제(顆粒劑), 산제, 세립제, 액제, 유탁제(乳濁濟) 또는 펠렛제일 수 있으나, 이에 제한되는 것은 아니다. 이들 제형은 유효 성분 이외에 희석제(예: 락토오스, 덱스트로오스, 수크로오스, 만니톨, 솔비톨, 셀룰로오스 또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 또는 폴리에틸렌 글리콜), 또는 결합제(예: 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스 또는 폴리비닐피롤리딘)를 함유할 수 있다. 경우에 따라 붕해제, 흡수제, 착색제, 향미제, 또는 감미제 등의 약제학적 첨가제를 함유할 수 있다. 상기 정제는 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, fine granules, solutions, emulsions or pellets, but are not limited thereto. It is not. These formulations may contain, in addition to the active ingredient, diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose or glycine), glidants (e.g. silica, talc, stearic acid or polyethylene glycol), or binders (e.g. magnesium aluminum Silicates, starch pastes, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose or polyvinylpyrrolidine). It may optionally contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, or sweeteners. The tablets can be prepared by conventional mixing, granulating or coating methods.
비경구 투여를 위한 제제는 주사제, 점적제, 로션, 연고, 겔, 크림, 현탁제, 유제, 좌제(坐劑), 패취 또는 분무제일 수 있으나, 이에 제한되는 것은 아니다.Formulations for parenteral administration may be, but are not limited to, injections, drops, lotions, ointments, gels, creams, suspensions, emulsions, suppositories, patches or sprays.
본 발명의 일측면에 따른 약학 조성물의 유효 성분은 투여 받을 대상의 연령, 성별, 체중, 병리 상태 및 그 심각도, 투여 경로 또는 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 적용량 결정은 당업자의 수준 내에 있으며, 이의 1일 투여 용량은 예를 들어 0.1mg/kg/일 내지 100mg/kg/일, 보다 구체적으로는 5 mg/kg/일 내지 50 mg/kg/일이 될 수 있으나, 이에 제한되는 것은 아니다.The active ingredient of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Dosage determination based on these factors is within the level of one skilled in the art and its daily dosage may be, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / kg. May be, but is not limited to.
본 발명의 일측면은 상기 피부 재생 촉진제를 포함하는 식품 조성물을 제공한다. 상기 식품 조성물은 피부 재생 효과를 가지며, 구체적으로 피부 상처 및 화상을 치유하고 흉터를 감소시킬 수 있다. One aspect of the present invention provides a food composition comprising the skin regeneration accelerator. The food composition has a skin regenerating effect and specifically can heal skin wounds and burns and reduce scars.
상기 식품 조성물의 제형은 특별히 한정되지 않으나, 예를 들어, 정제, 과립제, 분말제, 드링크제와 같은 액제, 캐러멜, 겔, 바 등으로 제형화될 수 있다. 각 제형의 식품 조성물은 유효 성분 이외에 해당 분야에서 통상적으로 사용되는 성분들을 제형 또는 사용 목적에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있으며, 다른 원료와 동시에 적용할 경우 상승 효과가 일어날 수 있다.The formulation of the food composition is not particularly limited, but may be, for example, formulated into a liquid such as tablets, granules, powders, drinks, caramels, gels, bars, and the like. In addition to the active ingredient, the food composition of each formulation may be suitably selected by a person skilled in the art according to the formulation or purpose of use in addition to the active ingredient, and may be synergistic when applied simultaneously with other raw materials.
상기 유효 성분의 투여량 결정은 당업자의 수준 내에 있으며, 이의 1일 투여 용량은 예를 들어 0.1mg/kg/일 내지 5000mg/kg/일, 보다 구체적으로는 50 mg/kg/일 내지 500 mg/kg/일이 될 수 있으나, 이에 제한되지 않으며, 투여하고자 하는 대상의 연령, 건강 상태, 합병증 등 다양한 요인에 따라 달라질 수 있다.Determination of the dosage of the active ingredient is within the level of those skilled in the art, the daily dosage of which is for example from 0.1 mg / kg / day to 5000 mg / kg / day, more specifically from 50 mg / kg / day to 500 mg / kg / day, but is not limited thereto, and may vary depending on various factors such as age, health condition, and complications of the subject to be administered.
이하, 실험예를 들어 본 발명의 구성 및 효과를 보다 구체적으로 설명한다. 그러나, 이들 실험예는 본 발명에 대한 이해를 돕기 위해 예시의 목적으로만 제공된 것일 뿐 본 발명의 범주 및 범위가 실험예에 의해 제한되는 것은 아니다.Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to experimental examples. However, these experimental examples are provided only for the purpose of illustration to help the understanding of the present invention is not limited to the scope and scope of the present invention.
[실험예 1] 각질형성세포에서 성장 인자의 세포 이동(cell migration) 효과 평가Experimental Example 1 Evaluation of Cell Migration Effect of Growth Factor in Keratinocytes
사람 유래의 각질형성세포(keratinocyte) 세포주인 HaCaT 세포를 10%의 소태아혈청(fetal bovine serum, JRH Bioscience, Tokyo, Japan), 100 mg/ml의 페니실린 및 100 mg/ml의 스트렙토마이신(모두 GIBCO, Milan, Italy에서 입수)을 첨가한 DMEM 배지(Invitrogen, Carlsbad, CA)를 이용하여 37℃, 5% CO2 조건에서 배양하였다. 배양한 세포를 각 웰 당 3.5 X 105이 되도록 12-웰 플레이트에 깔고, 하룻밤 동안 세포가 기벽에 붙기를 기다린 다음, PBS로 세포를 한번 세척하고 200 ㎕ 피펫 팁(pipet tip)으로 세포를 긁어 가운데에 수직선 모양의 스크래치(scratch)를 만들어 주었다. 떨어져 나간 세포 잔여물(cell debris)을 제거하기 위해 PBS로 2회 세척하고, 아래 표 1의 각 시험물질이 포함된 FBS-free DMEM으로 배지를 갈아주었다. 사진 촬영 시 항상 동일한 부분을 찍기 위해 웰 가운데를 미세한 마커로 표시하고 시험 시작(0시간)과 동시에 표시한 부분의 세포 사진을 찍었다. 마찬가지로 24시간 후의 세포 사진도 촬영하였다. 0시간과 24시간 후의 사진을 이미지 분석 프로그램, 멀티 게이지(Multi gauge, Fujifilm, Japan)로 분석하여 단일층 세포 위에 만들어진 스크래치 면적을 측정하였다. 세포 스크래치 면적을 측정한 후 다음의 수학식에 따라 스크래치 면적이 채워진 영역을 상처 충진율(wound fill percentage, %)로 나타내었다. 그 결과를 도 1에 나타내었다.HaCaT cells, human-derived keratinocyte cell lines, were treated with 10% fetal bovine serum (JRH Bioscience, Tokyo, Japan), 100 mg / ml penicillin and 100 mg / ml streptomycin (both GIBCO , DMEM medium (Invitrogen, Carlsbad, Calif.) Was added at 37 ℃, 5% CO 2 conditions. Incubate the cells in a 12-well plate at 3.5 X 10 5 per well, wait overnight for the cells to adhere to the wall, wash the cells once with PBS and scrape the cells with a 200 μl pipette tip. I made a vertical scratch in the middle. Washed twice with PBS to remove the cell debris that fell off, and the medium was changed to FBS-free DMEM containing each test substance in Table 1 below. In order to always take the same part at the time of taking the picture, the center of the well was marked with a fine marker, and at the same time as the start of the test (0 hours), a picture of the cell was taken. Similarly, the cell photograph after 24 hours was also taken. Photos after 0 and 24 hours were analyzed by an image analysis program, Multi gauge (Fujiga, Japan) to measure the scratch area on monolayer cells. After measuring the cell scratch area, the area filled with the scratch area was expressed as a wound fill percentage (%) according to the following equation. The results are shown in FIG.
[수학식 1][Equation 1]
상처 충진율 (%) = {(0시간 스크래치 면적 - 24시간 스크래치 면적)/ 0시간 스크래치 면적} X 100Wound Fill Rate (%) = {(0 Hour Scratch Area-24 Hour Scratch Area) / 0 Hour Scratch Area} X 100
표 1
Table 1
| EGF | TGF-β | PDGF-AA | bFGF | IGF-1 | 합계 | |
| 대조군 | 0 | 0 | 0 | 0 | 0 | 0.06ppm |
| EGF | 0.06ppm | 0 | 0 | 0 | 0 | 0.06ppm |
| TGF-β | 0 | 0.06ppm | 0 | 0 | 0 | 0.06ppm |
| PDGF-AA | 0 | 0 | 0.06ppm | 0 | 0 | 0.06ppm |
| bFGF | 0 | 0 | 0 | 0.06ppm | 0 | 0.06ppm |
| IGF-1 | 0 | 0 | 0 | 0 | 0.06ppm | 0.06ppm |
| EGF+TGF-β | 0.03ppm | 0.03ppm | 0 | 0 | 0 | 0.06ppm |
| EGF+PDGF-AA | 0.03ppm | 0 | 0.03ppm | 0 | 0 | 0.06ppm |
| EGF+FGF | 0.03ppm | 0 | 0 | 0.03ppm | 0 | 0.06ppm |
| EGF+IGF-1 | 0.03ppm | 0 | 0 | 0 | 0.03ppm | 0.06ppm |
| TGF-β+PDGF-AA | 0 | 0.03ppm | 0.03ppm | 0 | 0 | 0.06ppm |
| TGF-β+FGF | 0 | 0.03ppm | 0 | 0.03ppm | 0 | 0.06ppm |
| TGF-β+IGF-1 | 0 | 0.03ppm | 0 | 0 | 0.03ppm | 0.06ppm |
| PDGF-AA+FGF | 0 | 0 | 0.03ppm | 0.03ppm | 0 | 0.06ppm |
| PDGF-AA+IGF-1 | 0 | 0 | 0.03ppm | 0 | 0.03ppm | 0.06ppm |
| FGF+IGF-1 | 0 | 0 | 0 | 0.03ppm | 0.03ppm | 0.06ppm |
| EGF+TGF-β+PDGF-AA | 0.02ppm | 0.02ppm | 0.02ppm | 0 | 0 | 0.06ppm |
| EGF+TGF-β+FGF | 0.02ppm | 0.02ppm | 0 | 0.02ppm | 0 | 0.06ppm |
| EGF+TGF-β+IGF-1 | 0.02ppm | 0.02ppm | 0 | 0 | 0.02ppm | 0.06ppm |
| EGF+PDGF-AA+FGF | 0.02ppm | 0 | 0.02ppm | 0.02ppm | 0 | 0.06ppm |
| EGF+PDGF-AA+IGF-1 | 0.02ppm | 0 | 0.02ppm | 0 | 0.02ppm | 0.06ppm |
| EGF+FGF+IGF-1 | 0.02ppm | 0 | 0 | 0.02ppm | 0.02ppm | 0.06ppm |
| TGF-β+PDGF-AA+FGF | 0 | 0.02ppm | 0.02ppm | 0.02ppm | 0 | 0.06ppm |
| TGF-β+PDGF-AA+IGF-1 | 0 | 0.02ppm | 0.02ppm | 0 | 0.02ppm | 0.06ppm |
| TGF-β+FGF+IGF-1 | 0 | 0.02ppm | 0 | 0.02ppm | 0.02ppm | 0.06ppm |
| PDGF-AA+FGF+IGF-1 | 0 | 0 | 0.02ppm | 0.02ppm | 0.02ppm | 0.06ppm |
| EGF | TGF-β | PDGF-AA | bFGF | IGF-1 | Sum | |
| Control | 0 | 0 | 0 | 0 | 0 | 0.06 ppm |
| EGF | 0.06 ppm | 0 | 0 | 0 | 0 | 0.06 ppm |
| TGF-β | 0 | 0.06 ppm | 0 | 0 | 0 | 0.06 ppm |
| PDGF-AA | 0 | 0 | 0.06 ppm | 0 | 0 | 0.06 ppm |
| bFGF | 0 | 0 | 0 | 0.06 ppm | 0 | 0.06 ppm |
| IGF-1 | 0 | 0 | 0 | 0 | 0.06 ppm | 0.06 ppm |
| EGF + TGF-β | 0.03ppm | 0.03ppm | 0 | 0 | 0 | 0.06 ppm |
| EGF + PDGF-AA | 0.03ppm | 0 | 0.03ppm | 0 | 0 | 0.06 ppm |
| EGF + FGF | 0.03ppm | 0 | 0 | 0.03ppm | 0 | 0.06 ppm |
| EGF + IGF-1 | 0.03ppm | 0 | 0 | 0 | 0.03ppm | 0.06 ppm |
| TGF-β + PDGF-AA | 0 | 0.03ppm | 0.03ppm | 0 | 0 | 0.06 ppm |
| TGF-β + FGF | 0 | 0.03ppm | 0 | 0.03ppm | 0 | 0.06 ppm |
| TGF-β + IGF-1 | 0 | 0.03ppm | 0 | 0 | 0.03ppm | 0.06 ppm |
| PDGF-AA + FGF | 0 | 0 | 0.03ppm | 0.03ppm | 0 | 0.06 ppm |
| PDGF-AA + IGF-1 | 0 | 0 | 0.03ppm | 0 | 0.03ppm | 0.06 ppm |
| FGF + IGF-1 | 0 | 0 | 0 | 0.03ppm | 0.03ppm | 0.06 ppm |
| EGF + TGF-β + PDGF-AA | 0.02ppm | 0.02ppm | 0.02ppm | 0 | 0 | 0.06 ppm |
| EGF + TGF-β + FGF | 0.02ppm | 0.02ppm | 0 | 0.02ppm | 0 | 0.06 ppm |
| EGF + TGF-β + IGF-1 | 0.02ppm | 0.02ppm | 0 | 0 | 0.02ppm | 0.06ppm |
| EGF + PDGF-AA + FGF | 0.02ppm | 0 | 0.02ppm | 0.02ppm | 0 | 0.06 ppm |
| EGF + PDGF-AA + IGF-1 | 0.02ppm | 0 | 0.02ppm | 0 | 0.02ppm | 0.06 ppm |
| EGF + FGF + IGF-1 | 0.02ppm | 0 | 0 | 0.02ppm | 0.02ppm | 0.06 ppm |
| TGF-β + PDGF-AA + FGF | 0 | 0.02ppm | 0.02ppm | 0.02ppm | 0 | 0.06 ppm |
| TGF-β + PDGF-AA + IGF-1 | 0 | 0.02ppm | 0.02ppm | 0 | 0.02ppm | 0.06 ppm |
| TGF-β + FGF + IGF-1 | 0 | 0.02ppm | 0 | 0.02ppm | 0.02ppm | 0.06ppm |
| PDGF-AA + FGF + IGF-1 | 0 | 0 | 0.02ppm | 0.02ppm | 0.02ppm | 0.06ppm |
도 1에서 볼 수 있듯이, 각 성장 인자 및 성장 인자들의 조합은 각질형성세포의 재생을 촉진한다. 그 중에서도 상피 세포 성장 인자와 혈소판 유래 성장 인자-AA의 조합, 상피 세포 성장 인자 및 혈소판 유래 성장 인자-AA의 조합, 상피 세포 성장 인자, 형질 전환 성장 인자-β 및 혈소판 유래 성장 인자-AA의 조합, 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1의 조합, 그리고 형질 전환 성장 인자-β, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1의 조합이 특히 우수한 각질형성세포 재생 촉진 효과를 나타내었다. 이를 통해 성장 인자 또는 그들의 조합은 세포 재생을 촉진하여 피부 재생을 촉진하고 나아가 피부 상처 및 화상 치유를 촉진할 수 있음을 알 수 있다.As can be seen in Figure 1, each growth factor and combination of growth factors promotes the regeneration of keratinocytes. Among them, a combination of epithelial growth factor and platelet derived growth factor-AA, a combination of epithelial growth factor and platelet derived growth factor-AA, a combination of epithelial growth factor, transforming growth factor-β and platelet derived growth factor-AA. , Combination of epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth factor-1, and combination of transforming growth factor-β, platelet-derived growth factor-AA and insulin-like growth factor-1 It showed a cell regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
[실험예 2] 섬유아세포에서 성장 인자의 세포 이동(cell migration) 효과 평가Experimental Example 2 Evaluation of Cell Migration Effects of Growth Factors in Fibroblasts
사람의 피주 조직에서 분리한 섬유아세포(fibroblast)를 이용한 것을 제외하고는, 실험예 1과 실질적으로 동일한 방법으로 표 1의 성장 인자 및 그 조합을 처리한 세포의 상처 충진율(wound fill percentage, %)을 구하였다. 그 결과는 도 2에 나타내었다.Wound fill percentage (%) of cells treated with the growth factors and combinations thereof in Table 1 in substantially the same manner as in Experimental Example 1, except that fibroblasts isolated from human blood tissues were used. Was obtained. The results are shown in FIG.
도 2에서 볼 수 있듯이, 각 성장 인자 및 성장 인자들의 조합은 섬유아세포의 재생을 촉진한다. 그 중에서도 혈소판 유래 성장 인자-AA 및 섬유아세포 성장 인자의 조합, 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 섬유아세포 성장 인자의 조합, 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1의 조합, 그리고 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 섬유아세포 성장 인자의 조합이 특히 우수한 섬유아세포 재생 촉진 효과를 나타내었다. 이를 통해 성장 인자 또는 그들의 조합은 세포 재생을 촉진하여 피부 재생을 촉진하고, 나아가 피부 상처 및 화상 치유를 촉진할 수 있음을 알 수 있다.As can be seen in Figure 2, each growth factor and combination of growth factors promotes the regeneration of fibroblasts. Among them, a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, a combination of platelet-derived growth factor-AA and fibroblast growth factor, epithelial cell growth factor, platelet-derived growth factor-AA and insulin-like growth The combination of factor-1 and the combination of epithelial growth factor, platelet derived growth factor-AA and fibroblast growth factor showed a particularly good fibroblast regeneration promoting effect. It can be seen that growth factors or combinations thereof may promote cell regeneration to promote skin regeneration and further promote skin wound and burn healing.
[실험예 3] 인공피부의 상처부위에서의 피부 재생효능 평가Experimental Example 3 Evaluation of Skin Regeneration Efficacy in Wounds of Artificial Skin
인공피부에 CO2 레이저를 조사하여 열화상 상처를 만들고 여기에 상피 세포 성장 인자(EGF), 혈소판 유래 성장 인자-AA(PDGF-AA) 및 인슐린 유사 성장 인자-1(IGF-1)의 조합으로 이루어진 성장인자 조성물(growth factor mixture)을 처리하여, 상처회복 과정에서의 상처부위로의 각질형성세포 이동촉진 효과 (cytokeratin-10), 상처부위의 기저막(basement membrane) 합성 증진 효과 (Laminin α-5, Collagen IV), 상처부위의 진피 ECM(extra cellular matrix) 구성물질 발현 증가 효과(fibronectin)를 평가하였다.Infrared skin is irradiated with a CO 2 laser to create a thermal wound, which is a combination of epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1). By treating the growth factor mixture, the effect of promoting the migration of keratinocytes to the wound site (cytokeratin-10) and the enhancement of the basement membrane synthesis of the wound site (Laminin α-5) , Collagen IV), and the effect of increasing the expression of the extracellular matrix (ECM) components of the dermis (fibronectin) were evaluated.
먼저 인공피부(The EpiDermFT Full Thickness Skin Model, MatTek)를 인공피부전용 증식배지(growth media)에서 4일간 증식시키고, 인공피부에 CO2 레이저(eCO2, Lutronic)를 팁 타입(Tip Type) 120, 40mJ의 에너지, 8mm의 크기, 150 spots/cm2의 밀도조건으로 처리하여 상처를 만들었다. 그리고 이 인공피부를 총 3ppm 이하의 농도를 갖는 상피 세포 성장 인자(EGF), 혈소판 유래 성장 인자-AA(PDGF-AA) 및 인슐린 유사 성장 인자-1(IGF-1)의 조합으로 이루어진 성장인자 조성물(GF Mix.)과 4ppm의 상피 세포 성장 인자(EGF)가 각각 포함된 DMEM/F12 media와 성장인자를 처리하지 않은 DMEM/F12 media(대조군)에서 각각 배양시켰다.First, the EpiDermFT Full Thickness Skin Model (MatTek) was grown in growth media for artificial skin for 4 days, and CO 2 laser (eCO2, Lutronic) was applied to the artificial skin for tip type 120, 40mJ. The wound was made by treatment with an energy of 8 mm in size and a density of 150 spots / cm 2 . And a growth factor composition consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1) having a total skin concentration of 3 ppm or less. (GF Mix.) And DMEM / F12 media containing 4 ppm epidermal growth factor (EGF) and DMEM / F12 media (control) without growth factor, respectively.
1일째에 인공피부를 회수하여 O.C.T 화합물로 블록을 제작을 제작한 후, 크라이오스탯(Cryostat)으로 인공피부를 절편하여 사이토케라틴-10 염색으로 각질형성세포 이동을 관찰하고, 라미닌 α-5, 콜라겐 IV 면역염색으로 기저막의 합성을 관찰하였으며, 피브로넥틴 염색으로 진피 ECM 합성을 관찰하였다. 그리고 그 결과를 도 3에 나타내었다.On the first day, artificial skin was recovered, and a block was prepared using OCT compounds. Then, artificial skin was sectioned with cryostat, and keratinocyte staining was observed to observe keratinocytes. Laminin α-5, Synthesis of the basement membrane was observed by collagen IV immunostaining and dermal ECM synthesis was observed by fibronectin staining. The results are shown in FIG. 3.
도 3에서 볼 수 있듯이, 4ppm의 상피 세포 성장 인자(EGF)를 단독으로 처리한 인공피부보다, 본 발명의 일실시예로서 상피 세포 성장 인자(EGF), 혈소판 유래 성장 인자-AA(PDGF-AA) 및 인슐린 유사 성장 인자-1(IGF-1)의 조합으로 이루어진 성장인자 조성물(GF Mix.)을 총 3ppm 이하의 농도로 처리한 인공세포의 경우 표피뿐만 아니라 기저막(진피/표피 경계), 진피 모두에서 재생효과가 가장 우수한 것으로 나타났다. As can be seen in Figure 3, epithelial growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA) as an embodiment of the present invention than artificial skin treated with 4 ppm epidermal growth factor (EGF) alone ) And artificial base cells treated with a growth factor composition (GF Mix.) Composed of a combination of insulin-like growth factor-1 (IGF-1) at a concentration of 3 ppm or less in total, as well as the basement membrane (dermis / epidermal border) and dermis. The regeneration effect was found to be the best in all.
이는 본 발명의 일실시예인 상피 세포 성장 인자(EGF), 혈소판 유래 성장 인자-AA(PDGF-AA) 및 인슐린 유사 성장 인자-1(IGF-1)의 조합으로 이루어진 성장인자 조성물(GF Mix.)을 사용할 경우, EGF 등을 단독으로 사용하는 경우보다 더 적은 농도로도 보다 우수한 피부 재생 효능을 갖는 피부재생 촉진제를 제공할 수 있음을 의미한다.It is a growth factor composition (GF Mix.) Consisting of a combination of epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA) and insulin-like growth factor-1 (IGF-1), which is an embodiment of the present invention. When used, it means that it is possible to provide a skin regeneration accelerator having better skin regeneration efficacy even at a lower concentration than when using EGF alone.
본 발명의 일측면에 따른 조성물의 제형예를 아래에서 설명하나, 다른 여러 가지 제형으로도 응용 가능하며, 이는 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulation of the composition according to one aspect of the present invention will be described below, but can be applied to various other formulations, which are intended to explain in detail only, not intended to limit the invention.
[제형예 1] 연고의 제조Formulation Example 1 Preparation of Ointment
아래 표에 기재된 조성으로 통상의 방법에 따라 연고를 제조한다.Ointments are prepared according to conventional methods with the compositions described in the table below.
표 2
TABLE 2
| 성분 | 함량(중량%) |
| 정제수 | 잔량 |
| 글리세린 | 8.0 |
| 부틸렌그리콜 | 4.0 |
| 유동파라핀 | 15.0 |
| 베타글루칸 | 7.0 |
| 카보머 | 0.1 |
| 상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1 | 0.5 |
| 카프릴릭 카프릭 트리글리세라이드 | 3.0 |
| 스쿠알렌 | 1.0 |
| 세테아릴 글루코사이드 | 1.5 |
| 소르비탄 스테아레이트 | 0.4 |
| 스테아릴 알코올 | 1.0 |
| 방부제 | 적량 |
| 향 | 적량 |
| 색소 | 적량 |
| 밀랍 | 4.1 |
| ingredient | Content (% by weight) |
| Purified water | Remaining amount |
| glycerin | 8.0 |
| Butylene glycol | 4.0 |
| Liquid paraffin | 15.0 |
| Beta Glucan | 7.0 |
| Carbomer | 0.1 |
| Epithelial Cell Growth Factor, Platelet-derived Growth Factor-AA and Insulin-like Growth Factor-1 | 0.5 |
| Caprylic Capric Triglycerides | 3.0 |
| Squalene | 1.0 |
| Cetearyl Glucoside | 1.5 |
| Sorbitan stearate | 0.4 |
| Stearyl alcohol | 1.0 |
| antiseptic | Quantity |
| incense | Quantity |
| Pigment | Quantity |
| beeswax | 4.1 |
[제형예 2] 크림Formulation Example 2 Cream
아래 표에 기재된 조성으로 통상의 방법에 따라 크림을 제조한다.A cream is prepared according to a conventional method with the composition described in the table below.
표 3
TABLE 3
| 성분 | 함량(중량%) |
| 상피 세포 성장 인자, 인슐린 유사 성장 인자-1, 혈소판 유래 성장 인자-AA 및 섬유아세포 성장 인자 | 8.0 |
| 폴리에틸렌글리콜 모노스테아레이트 | 2.0 |
| 모노스테아르산 글리세린 | 5.0 |
| 세틸알코올 | 4.0 |
| 스쿠알렌 | 3.0 |
| 트리2-에틸헥산글리세릴 | 6.0 |
| 스핑고당지질 | 1.0 |
| 1,3-부틸렌글리콜 | 7.0 |
| 정제수 | 잔량 |
| ingredient | Content (% by weight) |
| Epithelial growth factor, insulin-like growth factor-1, platelet-derived growth factor-AA and fibroblast growth factor | 8.0 |
| Polyethylene Glycol Monostearate | 2.0 |
| Glycerin Monostearate | 5.0 |
| Cetyl alcohol | 4.0 |
| Squalene | 3.0 |
| Tri2-ethylhexaneglyceryl | 6.0 |
| Sphingolipid | 1.0 |
| 1,3-butylene glycol | 7.0 |
| Purified water | Remaining amount |
[제형예 3] 정제Formulation Example 3 Tablet
상피 세포 성장 인자, 인슐린 유사 성장 인자-1, 형질 전환 성장 인자-β 및 혈소판 유래 성장 인자-AA 7 mg, 대두 추출물 50 mg, 포도당 100 mg, 홍삼 추출물 50 mg, 전분 96 mg 및 마그네슘 스테아레이트 4 mg을 혼합하고 에탄올을 첨가하여 과립을 형성한 후 건조하고 정제로 타정한다.Epithelial growth factor, insulin-like growth factor-1, transforming growth factor-β and platelet derived growth factor-AA 7 mg, soybean extract 50 mg, glucose 100 mg, red ginseng extract 50 mg, starch 96 mg and magnesium stearate 4 The mg is mixed and ethanol is added to form granules, then dried and tableted.
[제형예 4] 건강 음료Formulation Example 4 Healthy Drinks
상피 세포 성장 인자, 혈소판 유래 성장 인자-AA 및 인슐린 유사 성장 인자-1......................... 100 g Epithelial Cell Growth Factor, Platelet-derived Growth Factor-AA and Insulin-like Growth Factor-1 ... 100 g
구연산................................ 1000 ㎎ Citric Acid ................................... 1000 mg
올리고당................................ 100 g Oligosaccharide ......................... 100 g
타우린.................................... 1 g Taurine .................................... 1 g
정제수................................. 적량 Purified water .....
통상의 건강 음료 제조 방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균한다.The above ingredients are mixed according to a conventional method for preparing a health beverage, then stirred and heated at 85 ° C. for about 1 hour, and then the resulting solution is filtered and sterilized.
Claims (7)
- 상피 세포 성장 인자(EGF, Epidermal growth factor), 혈소판 유래 성장 인자-AA(PDGF-AA, Platelet-derived growth factor-AA) 및 인슐린 유사 성장 인자-1(IGF-1, Insulin-like growth factor 1)을 포함하는 피부 재생 촉진제.Epidermal growth factor (EGF), Platelet-derived growth factor-AA (PDGF-AA) and Insulin-like growth factor 1 (IGF-1) Skin regeneration promoter comprising a.
- 제 1 항에 있어서,The method of claim 1,형질 전환 성장 인자-β(TGF-β, Transforming growth factor beta) 및 섬유아세포 성장 인자(FGF, Fibroblast growth factor) 중 하나 이상의 성장 인자를 더 포함하는 피부 재생 촉진제.A skin regeneration accelerator further comprising one or more growth factors of transforming growth factor-β (TGF-β, Transforming growth factor beta) and fibroblast growth factor (FGF).
- 제 1 항에 있어서,The method of claim 1,피부 상처 치유를 촉진하는 피부 재생 촉진제.Skin regeneration accelerators to promote skin wound healing.
- 제 1 항에 있어서,The method of claim 1,화상 치유를 촉진하는 피부 재생 촉진제.Skin regeneration accelerators that promote burn healing.
- 제 1 항에 있어서,The method of claim 1,각질형성세포 또는 섬유아세포의 재생을 촉진하는 피부 재생 촉진제.A skin regeneration promoter for promoting regeneration of keratinocytes or fibroblasts.
- 제 1 항 내지 제 5 항 중 어느 한 항에 따른 피부 재생 촉진제를 포함하는 화장료 조성물.A cosmetic composition comprising the skin regeneration accelerator according to any one of claims 1 to 5.
- 제 1 항 내지 제 5 항 중 어느 한 항에 따른 피부 재생 촉진제를 포함하는 약학 조성물.A pharmaceutical composition comprising the skin regeneration accelerator according to any one of claims 1 to 5.
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